Phase 3 randomized controlled trials (RCTs), while the gold standard for treatment efficacy and safety, are not always feasible, are expensive, can be prolonged and can be limited in generalizability. Other under-recognized sources of evidence can also help advance drug development. Basic science, proof-of-concept studies and early-phase RCTs can provide evidence regarding the potential for clinical benefit. Real-world evidence generated from registries or observational datasets can provide insights into the treatment of rare diseases that often pose a challenge for trial recruitment. Pragmatic trials embedded in healthcare systems can assess the treatment effects in clinical settings among patient populations sometimes excluded from trials. This Perspective discusses potential sources of evidence that may be used to complement explanatory phase 3 RCTs and to speed the development of new cardiovascular medications. Content is derived from the 19th Global Cardiovascular Clinical Trialists meeting (December 2022), involving clinical trialists, patients, clinicians, regulators, funders and industry representatives.
In literature and the humanities, guilt has the same major importance as in penal law. Due to the anthropocentric legal system, however, guilt is the linchpin par excellence within the framework of penal law. The article confirms this emphasis on guilt through an examination of the constitutional determinants of penal law, the development of the concept of guilt, and also a change in its perspective which has shifted to an emphasis on the purpose of punishment rather than on the reasons for it. Penal law is intended to ensure legal peace and map out a path for reconciliation within society.
